Resistance to herpes simplex virus-Type 1, the causative agent of acute gingivo-stomatitis and recurrent herpes labialis is under polygenic control. Using recombinant inbred strains, we have already identified one major gene responsible for resistance which appears to be on Chromosome 1, linked to the gene which controls expoxide hydrase. We are currently investigating the number, location and resistance mechanisms controlled by these genes. We plan to confirm this linkage in other inbred strains and by formal backcross analysis. The identification of this resistance gene will allow us to better study the role of the immune response in limiting infection by Herpes viruses. Results from these studies will aid in prevention and therapy of HSV infections in man.